Aggregation of the Amphipathic Peptides (AAKA)_n into Antiparallel β-Sheets

Helical wheel projections of peptides based on the repeating unit Ac-(AAKA)_n-NH₂ clearly illustrate an amphipathic nature. One should therefore expect these peptides to form helices if the number of residues exceeds a certain threshold value. Indeed, ECD measurements show that Ac-(AAKA)₄-NH₂ and, to a minor extent, also Ac-(AAKA)₃-NH₂ exhibit some helical content at millimolar concentrations in aqueous solution. Surprisingly, however, these peptides were found to form hydrogels with an antiparallel β-sheet conformation at centimolar concentrations. This occurs despite the positively charged lysine side chain which would be expected to inhibit the formation of extended β-sheet layers.